Lab Findings Support Provocative Theory On Cancer 'Enemy' Within

The white arrows in these two tumor samples point to a subset of tumor cells that are in a resting state.

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Originally published on August 1, 2012 4:54 pm

Scientists reported new evidence Wednesday that supports a provocative theory about cancer.

Three separate teams of scientists said they had, for the first time, shown that so-called cancer stem cells can be found naturally in brain tumors and early forms of skin and colon cancer.

Evidence has been mounting in recent years for the existence of these cells, which would be especially insidious. They are believed to resist standard chemotherapy and radiation and fuel the growth of tumors and relapses.

"After a tumor is treated by many conventional forms of therapy, the non-stem cells in a cancer are wiped out but the cancer stem cells may survive and thereafter regenerate an entirely new tumor, leading to what one calls clinical relapse," said Robert Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research in Boston.

The existence of these cells has been highly controversial. The evidence came mostly from manipulating cancer cells in laboratory dishes and transplanting human cancer cells into animals. It remained far from clear whether they really occurred on their own and for all types of cancers.

The new experiments set out to answer some of those doubts by studying cancers that occur naturally in laboratory mice.

"This was the first example of examination of a spontaneously growing tumor in its normal site of development where we were able to trace the existence of cancer stem cells," said Luis Parada, a professor of developmental biology at the University of Texas Southwestern Medical Center.

Parada and his colleagues performed a series of experiments in which they used sophisticated genetic techniques to trace and analyze brain tumor cells in mice. Two other teams in Europe conducted similar tests, but this time with early forms of either skin cancer or colon cancer.

All the research is being published this week in three papers in the journals Nature and Science.

"With these three studies we can say that in fact three different kinds of tumors adhere to the cancer stem cell hypothesis," Parada said.

Even though the studies were done in mice, Weinberg, Parada and others say there's no reason to think the findings don't apply to people. And if that's the case, the research could lead to new ways to fight cancer.

"It means that we've identified the enemy, finally," he said.

The key to defeating this enemy may be new drugs that specifically target these cancer stem cells.

"Previously we thought all we needed to do was kill off all the cells in the tumor without having any recognition of the existence of these subpopulations of cancer stem cells," Weinberg said. "Now we come to realize that both the non-stem cells and the stem cells need to be eliminated in a tumor in order for one to have a durable clinical response, which may eventually lead actually to a cure."

But not everyone is convinced. Some scientists remain skeptical that what the researchers have found are really cancer stem cells, or that they exist for all forms of cancer.

"The main issue is, 'Can you prove that these things exist? And that means considering the range of alternative explanations and disproving each one — one after another. And that's just not being done," said Scott Kern, who studies the genetics of cancer at Johns Hopkins. "I think the field has not matured."

"These three studies add further impetus to us moving ahead with these trials to try to eliminate these cancer stem cells in the hope that it will improve the outcome for patients with a variety of different kinds of cancer," said Max Wicha, who is studying some of the experimental medicines at the University of Michigan.

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Transcript

AUDIE CORNISH, HOST:

Now, to a provocative theory about cancer. It could explain why cancer patients suffer relapses. The theory says there is a special type of cancer cell hiding in the body, that can survive standard chemotherapy and radiation. NPR's Rob Stein has this story about new research that supports the theory.

ROB STEIN, BYLINE: Evidence has been mounting, in recent years, for the existence of an especially insidious kind of cancer cell. They're called cancer stem cells. These aren't the embryonic stem cells that have been getting so much attention in recent years. But like embryonic stem cells, they're also very immature cells with interesting powers.

Robert Weinberg is a cancer biologist at MIT. He says these cancer stem cells seem to act like seeds for tumors.

ROBERT WEINBERG: After a tumor is treated by many conventional forms of therapy, the non-stem cells in the cancer are wiped out. But the cancer stem cells may survive, and thereafter regenerate an entirely new tumor, leading to what one calls clinical relapse.

STEIN: These relapses are what doctors call recurrences, or metastases. They're often much harder to treat than the original tumors, and they're what eventually kills many cancer patients. But the existence of these cells has been highly controversial. The new experiment set out to answer some of these doubts. Luis Parada led one of the studies, at the University of Texas.

LUIS PARADA: This was the first example of examination of a spontaneously growing tumor in its normal site of development, where we were able to trace the existence of cancer stem cells.

STEIN: Parada and his colleagues performed a series of experiments. They used sophisticated genetic techniques to trace and analyze brain tumor cells in mice. Two other teams in Europe conducted similar studies, but this time with early forms of either skin cancer or colon cancer. All the research is being published this week in three papers, in the journals "Nature" and "Science."

PARADA: With these three studies, we can say that in fact, three different kinds of tumors adhere to the cancer stem cell hypothesis.

STEIN: Even though the studies were done in laboratory mice, Weinberg, Parada and others say there's no reason to think the findings don't apply to people as well. And if that's the case, the new research could lead to new ways to fight cancer.

PARADA: It means that we've identified the enemy, finally.

STEIN: The key to defeating this enemy may be a whole new class of drugs that specifically target these cancer stem cells. Here's Robert Weinberg at MIT again.

WEINBERG: Previously, we thought all we needed to do is kill off all the cells in the tumor, without having any recognition of the existence of these sub-populations of cancer stem cells. Now, we come to realize that both the non-stem cells, and the stem cells, need to be eliminated in the tumor in order for one to have a durable clinical response - which may eventually lead, actually, to a cure.

STEIN: But not everyone is convinced. Some scientists remain skeptical that what the researchers have found are really cancer stem cells. Scott Kern studies cancer genetics at Johns Hopkins. He says the new data falls far short of being conclusive.

SCOTT KERN: The main issue is, can you prove that these things exist? And that means considering the range of alternative explanations and disproving each one, one after another. And that's just not being done. I think that the field has not matured.

STEIN: Despite the skeptics, drug companies have already started designing drugs to target cancer stem cells. Max Wicha, of the University of Michigan, is testing some of them.

MAX WICHA: These three studies add further impetus to us moving ahead with these trials, to try to eliminate these cancer stem cells in the hope that it will improve the outcome for patients with a variety of different kinds of cancer.

STEIN: So scientists will continue to search for more conclusive evidence of the existence of these cancer stem cells, and look for new ways to kill them without harming the patients themselves. Rob Stein, NPR News. Transcript provided by NPR, Copyright NPR.